EP0035518A1 - Cohesive nonsticky electrically conductive gel composition. - Google Patents
Cohesive nonsticky electrically conductive gel composition.Info
- Publication number
- EP0035518A1 EP0035518A1 EP80901684A EP80901684A EP0035518A1 EP 0035518 A1 EP0035518 A1 EP 0035518A1 EP 80901684 A EP80901684 A EP 80901684A EP 80901684 A EP80901684 A EP 80901684A EP 0035518 A1 EP0035518 A1 EP 0035518A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- gel
- electrically conductive
- electrode
- skin
- conductive gel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0472—Structure-related aspects
- A61N1/0492—Patch electrodes
- A61N1/0496—Patch electrodes characterised by using specific chemical compositions, e.g. hydrogel compositions, adhesives
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01B—CABLES; CONDUCTORS; INSULATORS; SELECTION OF MATERIALS FOR THEIR CONDUCTIVE, INSULATING OR DIELECTRIC PROPERTIES
- H01B1/00—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors
- H01B1/06—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of other non-metallic substances
- H01B1/12—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of other non-metallic substances organic substances
- H01B1/122—Ionic conductors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0408—Use-related aspects
- A61N1/0456—Specially adapted for transcutaneous electrical nerve stimulation [TENS]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0408—Use-related aspects
- A61N1/046—Specially adapted for shock therapy, e.g. defibrillation
Definitions
- the present invention relates generally to electrically conductive gels which are used to transmit an electrical signal between the human skin and an electrode attached to an electrical recording or stimulating device.
- Such contact may be for the purpose of measuring electrical signals, as in the making of electrocardiograms or electroencephalograms, or applying electrical impulses to the body during electrotherapy.
- the skin is a difficult structure with which to make reliable, low resistance, electrical contact. Accordingly, it has become customary in the art to utilize a conductive medium between the electrode and the skin to enhance conductivity. This medium normally takes, the form of a conductive paste or gel which makes intimate contact with the skin, by conforming to the contours of the skin, and fills the gaps between the skin and the electrode, thus providing a more reliable path for the electrical current than is afforded by dry surface contact between electrode and skin.
- These gels or pastes are normally made of a thickened aqueous mixture containing a conductive salt, such as sodium chloride.
- Conventional thickening agents typically include polymers, such as polyvinylalcohol (commonly referred to as PVA), polyethylene glycol or polypropylene glycol; glycerol and glycerol derivatives, such as glycerol monostearate; and a number of naturally occurring gummy materials, such as gum tragacanth, sodium alginate, locust bean gum and guar gum.
- PVA polyvinylalcohol
- glycerol and glycerol derivatives such as glycerol monostearate
- gummy materials such as gum tragacanth, sodium alginate, locust bean gum and guar gum.
- a number of synthetic gummy materials and thickeners have also been used, including carboxymethyl cellulose, and proprietary materials such as Ganatrez materials sold by General Aniline and Film Corporation and
- German Offenlegangschrift 27 27 396 discloses a viscoelastic conductive gel comprising a high molecular weight polysaccharide and a polyol, which is said to leave behind no residue on the skin.
- the gels disclosed therein are not crosslinked, have a low water content, are capable of carrying little salt and require the use of high molecular weight (at least about 10 6 ) polysaccharides in order to provide the necessary cohesivity to be removed without leaving a residue.
- high molecular weight at least about 10 6
- the gels of the present invention are an improvement over prior art gels. They maintain themselves as a cohesive mass without the need for mechanical reinforcement. They do not leave a residue on the skin or the electrode. Furthermore, they are capable of tolerating high concentrations of salt without breakdown of the gel.
- the gels of the present invention are less expensive to produce than the gels of the prior art since they can contain relatively less thickener and more water while still maintaining sufficient cohesive strength.
- the present invention provides an electrically conductive gel for use in establishing a low resistance contact between an electrode and a biological body, comprising an aqueous solution of a natural gum capable of crosslinking and a crosslinking agent.
- the gum and crosslinking agent are present in quantities sufficient to impart a gel-like body to the material and to provide the electrically conductive gel with sufficient internal strength to remain cohesive without reinforcement.
- the gel material is capable of containing up to saturated concentrations of ionized salt without breakdown of the crosslinked gel.
- the gel material is nonsticky in character.
- the gel of the instant invention provides a conductive, conformable interface between the skin and the electrodes placed thereon, thus preventing electrical noise interference; additionally it is easy to apply, removable without leaving a residue, and has sufficient strength to perform well without reinforcement.
- cohesive should be interpreted to mean that the gel has more adhesion to itself than to the surface of the skin and, thus, is capable of maintaining internal integrity and lifting from the skin without leaving a residue.
- the instant invention provides a gel which conducts small electrical signals faithfully and which produces no artifacts of its own to degrade the signal.
- the gel is physically stable over a wide temperature range, i.e., its flow and cohesive properties are essentially the same over the range of 0 to 60°C.
- the gel of the present invention is resistant to drying out.
- the gel can be used routinely with a minimum of irritation to the skin.
- the gels of the present invention are stable in the presence of any practical salt concentration.
- the crosslinked gels of the present invention will not break down.
- This feature is in contrast to crosslinked gels based on polyvinyl chloride which will break down in the presence of salt concentrations much lower than saturation, i.e., a percent NaCl higher than about 5 percent.
- the gel is not adversely affected by exudates from the skin, such as perspiration.
- the gels of the present invention can be used as a conductive medium on a patient's skin before emplacing an electrode or in a pre-assembled electrode. An example of the former use is in emergency situations where a patient is suffering from cardiac distress.
- Dabs of gel are dispensed onto the patient's skin in a standard pattern over the heart area. Electrodes are attached to these portions and are connected to an electrocardiograph, the read-out of which, commonly called an E.C.G., provides an indication of the patient's heart condition.
- an E.C.G. electrocardiograph
- the gel for long-term monitoring of heart-function it is preferred to use the gel in a pre-assembled electrode, referred to as a "monitoring electrode".
- Such an electrode comprises an electrode plate having on one surface thereof means for electrical connection to an electro-medical apparatus and on the opposite, body contacting surface thereof, the electrically conductive gel material of the present invention. In both uses the gel is applied and electrical contact achieved with light finger pressure. After use the gel may simply be lifted off the skin in a cohesive mass without leaving a sticky residue.
- the gel of this invention is particularly useful as a conductive medium between the skin and a biopotential monitoring electrode suitable for detecting the very small electrical signals, such as are characteristic of E.C.G. measurements, it is not limited to this use.
- the gel can be used as the conductive medium between defibrillation electrodes and the skin of a patient whose heart is in fibrillation. In such a case high voltages are required in order to electrically shock the heart into beating.
- a major advantage of the new gel in this use is that it does not smear or flow rapidly over a surface, thus avoiding the creation of a potentially dangerous conductive path; possibly over a patient's chest.
- An added advantage of the gel of the present invention is the greatly reduced chore of cleanup. Since the electrodes used in defibrillation are large, a substantial proportion of the patient's chest can become covered with conductive medium.
- the cohesive, non-sticky gel of the present invention greatly eases clean-up of the patient.
- Another use of the present invention is as an electroconductive medium for an electrosurgical ground plate.
- Still another use of the present gel is as the conductive medium between the skin and electrodes of the type used for transcutaneous nerve stimulation or for pain relief. These electrodes are often in the form of metal plates or foils.
- the preferred embodiment of the gel has limitations in conditions where it is under pressure.
- the compositions have the ability to cold flow; that is, when placed in a vessel the gum will eventually acquire the shape of the inside of the vessel. By this means, the ability of the gel to conform accurately to the contours of, for example, the skin and the undersurface of an electrode, is assured. In practice, a momentary light finger pressure is all that is required to emplace an electrode properly on the skin.
- the gel will spread slowly under pressure, and if squeezed for a long time, such as when placed under a supine patient undergoing lengthy surgery, it could be squeezed out beyond the immediate area of the electrode plate. Under these conditions, a restraining means can be used to keep the gel in place.
- a porous fibrous material such as a pouch of inert porous woven or nonwoven fabric placed around the gel can be used as a restraining means.
- An open-cell foam, such as one of the polyurethane foams, impregnated with the gel may also be used.
- the present invention provides an electrolyte gel based on a crosslinked natural gum as the thickening agent.
- the preferred gums are guar gum and locust bean gum.
- the useful natural gums are high polymeric saccharides comprised of hexose, pentose or uronic acid groups linked together.
- One feature of the natural gums is their ready availability and low cost.
- a feature of guar gum is that it can be obtained in a rather pure state without extensive processing. Guar gum in its natural state is relatively pure, having very few impurities such as sulphur (sometimes found in agar) or extraneous ions (as found in many of the less pure gums).
- guar gum gels of this invention are useful practical features of guar gum gels. They can be produced at room temperature or at only slightly raised temperature due to the fact that guar gum powder mixes well with room temperature water unlike synthetic gels such as polyvinyl alcohol which requires heating and more complicated production techniques.
- the natural pH of guar gum gels of this invention is approximately 7-8.5, which is an excellent pH range for a composition to be used against the skin since it is close to the physiological pH. Gels of the prior art have been neutralized or buffered in order to achieve an acceptable pH.
- Natural gums are polysaccharides obtained from natural substances.
- guar gum is a polysaccharide obtained from the seeds of the guar plant.
- the structure of guar gum, as illustrated below, is that of a chain mannose sacharide polymer with repeating single-unit galactose branches, referred to as galactomannan.
- Guar gum is available in anionic, cationic and nonionic forms.
- the nonionic type has been found most suitable for use with Ag/AgCl electrodes and is preferred for use with sensitive biomonitoring electrodes.
- Applicant has surprisingly found that gels made from a hydroxypropylated nonionic guar gum, sold by the Stein Hall Co. under the trademark JAGUAR® HP-11, are stable to concentrations of chloride ion greater than 10 percent by weight. Thus, this guar gum gel can be successfully utilized where the transmission of high currents is desired (i.e., high salt concentrations are required) without breakdown of the gel's cohesive structure.
- crosslinkable natural gums with other thickeners are also within the scope of the present invention.
- PVA polyvinyl alcohol
- This formulation is not particularly advantageous for biomonitoring electrodes, but can be valuable in electrodes where the gel is under high compressive loads, such as in electrosurgery or in transcutaneous nerve stimulation.
- Other thickeners which can be mixed with the crosslinkable natural gums include hydroxyethyl cellulose, and hydroxy- propyl methyl cellulose.
- examples of other natural gums which can be mixed with the crosslinkable natural gums of the present invention include gum arabic, sodium alginate and gum tragacanth.
- the gels of the present invention have increased internal cohesiveness and are able to be easily removed from surfaces with which they come in contact due to their crosslinked nature.
- the preferred crosslinking agent is borate ion, supplied by potassium tetraborate or sodium tetraborate. Borate ion reacts effectively with the preferred gums, guar gum and locust bean gum, to form stable gels.
- compositions crosslinked with borate are acceptable for contact with human skin.
- crosslinking agents useful in the gels of the present invention include salts, such as ferric chloride, calcium chloride and the acetates of the multivalent cations of lead, chromium or nickel.
- salts such as ferric chloride, calcium chloride and the acetates of the multivalent cations of lead, chromium or nickel.
- reaction conditions e.g., temperature, pH, agitation. time of reaction, etc.
- Such crosslinking can be detected by viscosity changes or by gel formations.
- the difficulty in preparing a stable medically-acceptable gel makes the above means of crosslinking less desirable than the borate-guar system.
- the preferred embodiment of the present invention includes within the crosslinked gum, any salt suitable to act as a conductor for the passage of electric current from an electrode to the body of a patient.
- crosslinked gums containing no salt are also contemplated since the gels of the present invention are aqueous in major portions and can conduct a current when subjected to high voltages.
- the preferred salts are chlorides, particularly those of sodium or potassium, since these are the most compatible with the normal electrolytes within the body.
- the chlorides are particularly preferred for use with the very sensitive Ag/AgCl (silver/silver chloride) electrodes, as they take part in the cell reaction and contribute to the proper functioning of the electrode.
- the Ag/AgCl electrodes are particularly well suited for measuring minute electrical bio-events.
- the electrolyte concentration is important, as it affects both current carrying capacity and skin irritation.
- a surprising feature of the crosslinked gels of the present invention are their stability even in the presence of saturated sodium chloride, approximately 25 percent by weight.
- the present invention provides a gel which is stable in the presence of essentially any salt concentration desired.
- Electrode storage time is another factor in the determination of electrolyte type and concentration.
- Lower salt concentrations are preferred when electrodes are to be stored a long time between manufacture and use.
- Salt solutions of sodium chloride and potassium chloride are corrosive to ferrous metals, with the result that gels high in concentrations of these salts may corrode the electrodes when in contact with the electrodes over a sufficiently long period of time.
- salts less corrosive than sodium chloride or potassium chloride, such as sodium citrate should be used.
- the choice of electrolyte is also affected by electrode composition.
- Electrodes made of aluminum, stainless steel or German silver are employed for biomonitoring purposes spurious signals or electrical noise are commonly experienced. Such signals are thought to be generated by chemical reactions taking place between the electrode and corrosive conductive salts, such as sodium chloride. Potassium citrate can be substituted for more corrosive salts, in order to reduce electrical noise.
- Another aspect of the present invention may include the presence of humectants, plasticizers, and wetting agents in the crosslinked gel. Humectants increase the ability of the gel to resist drying out when exposed to the atmosphere or to conditions of low humidity. Plasticizers add smoothness and increased pliability to the gel.
- wetting agents permit the gel powder to disperse in water in a homogeneous and lump-free manner.
- 1,3-butylene glycol, tetrahydrofurfuryl alcohol and dipropylene glycol are known plasticizers and humectants.
- Diethylene glycol and glycerol have been commonly utilized as humectants.
- glycerol competes with guar gum for borate, and can interfere with proper gel formation by inhibiting crosslinking if present in sufficient quantity.
- Propylene glycol can function in the gels of the present invention as a humectant, a plasticizer and a wetting agent for guar gum powder during manufacture.
- the gels of the present invention may also contain preservatives to prevent bacterial growth during storage and use.
- the parabens e.g., methyl and propyl- p-hydroxybenzoates, are well-accepted preservatives for use in medicinal preparations.
- Raising the amount of guar gum increases the viscosity of the gel, and conversely lowering the amount of guar gum decreases the viscosity of the gel.
- Raising the chloride ion concentration increases the electrical conductivity of the gel and decreases the gel-skin impedance, and conversely lowering the chloride ion concentration decreases the electrical conductivity of the gel and increases gel-skin impedance.
- Raising the borate ion concentration increases the degree of crosslinking and the stiffness of the gel, and conversely lowering the borate ion concentration decreases the degree of crosslinking and thus the stiffness of the gel.
- Raising the amount of propylene glycol, a humectant, increases the ability of the gel to resist drying out.
- Raising the concentration of the parabens increases the bacteriostatic ability of the gel.
- composition for use in the practice of the present invention is the following:
- This composition has excellent electrical properties in addition to a useful combination of physical properties.
- the gel makes good contact with both skin and electrode, is stable with regard to moisture loss (a major factor affecting shelf-life and useful life on patient), and possesses excellent cohesive strength.
- Example 1 Approximately 300 ml of distilled water is heated in a 600 ml beaker to a temperature of 60°-75o C. and 9.9 gm of sodium chloride is added to the heated water with stirring until dissolved. In a separate vessel, 0.16 gm of propyl-p-hydroxy benzoate and 0.8 gm of methyl-p-hydroxy benzoate are mixed well with 80.0 gm of propylene glycol until dissolved. To this mixture 6.4 gm of JAGUAR® HP-11 is added slowly with constant stirring until homogeneously dispersed.
- the dispersion of guar gum in paraben/propylene glycol solution is added slowly to the aqueous sodium chloride solution with vigorous stirring, e.g., with a high shear mixer (Homo-mixer commercially available from Gifford Wood, Inc., Hudson, N.Y.). Vigorous mixing is continued and the temperature is maintained at about 60°-75o C. until the mixture is smooth and the guar gum is completely dissolved (about 10-20 minutes). The resultant mixture is a homogeneous, viscous solution. The heat source is removed and vigorous mixing is continued while 20 ml of a 10% w/v solution of potassium tetraborate is slowly added. The stirring is discontinued and the mixture is allowed to cool to room temperature.
- a high shear mixer Homo-mixer commercially available from Gifford Wood, Inc., Hudson, N.Y.
- Vigorous mixing is continued and the temperature is maintained at about 60°-75o C. until the mixture is smooth and the guar gum is completely dissolved
- Examples 6 and 7 illustrate that a gel can be made according to the present invention which can accommodate high salt concentrations.
- Example 8 Approximately 300 ml of distilled water is heated in a 600 ml beaker to a temperature of 60°-75° C. 9.9 gm of sodium chloride, 0.16 gm of propyl-p-hydroxy benzoate and 6.4 gm of guar gum powder (commercially available as JAGUAR® A2S from the Stein Hall Co.) are added to the water and the mixture is stirred vigorously, e.g., with a Homo-mixer, until a homogeneous mixture is obtained (15-20 minutes).
- JAGUAR® A2S commercially available as JAGUAR® A2S from the Stein Hall Co.
- the heat source is removed and, using moderate stirring (e.g., with a propeller-type stirrer), a 10% w/v solution of potassium tetraborate, and propylene glycol are slowly added in alternate aliquots over a period of about 5-10 minutes as follows:
- Example 9 Following the procedure of Example 8 a gel was prepared having the following composition:
- Example Amount Gum tetraborate Nacl Number Gum (% by wt. ) (% by wt. ) (% by wt.
- Table I is a list of the physical properties of the gels of Examples ( 1-9 ) .
- Resistivity measurements were taken at 10KHz (sinusoidal signal) using a Hewlett Packard Model 4800 A vector impedance meter. A 10KHz frequency was chosen to minimize electrode polarization effects. The cell was filled with the appropriate gel and its measured resistance (Rm) was obtained. Resistivity ( p ) is given in ohm-cm by the equation
- Example 10 A 1.6% by weight solution of JAGUAR® HP-11 in distilled water was prepared. To a 40 c.c. sample of the guar gum solution approximately 1 c.c. of a 10% by weight solution of FeCl 3 in water was added with stirring. To this a concentrated solution of potassium hydroxide was added dropwise and the pH of the mixture was monitored. When the pH rose to an alkaline pH of about 11.2, from a starting pH of about 2.25, a crosslinked, cohesive, non-sticky gel was obtained.
- Example 11 A 1.6% by weight solution of JAGUAR® CMHP in distilled water was prepared. To a 20 gm sample of the guar gum solution, 15 drops of a 10% by weight solution of chromium acetate was added with stirring. A concentrated solution of potassium hydroxide was then added dropwise to the mixture with stirring and the pH was monitored. At an alkaline pH of above about 9, an excellent crosslinked gel of the present invention was obtained. Subsequently 20 drops of a saturated solution of potassium chloride was mixed with the gel. The gel remained crosslinked, cohesive and non-sticky.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Radiology & Medical Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
- Cosmetics (AREA)
- Colloid Chemistry (AREA)
- Conductive Materials (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
Un gel cohesif non collant electriquement conducteur facilite le contact de faible resistance entre une electrode metallique et un corps biologique. Le gel comprend une solution aqueuse ayant des concentrations de saturation de sels ionises comme agent conducteur, une gomme naturelle capable de reticulation, et un materiau de reticulation qui donne au gel electriquement conducteur une resistance interne suffisante pour garder sa cohesion sans renforcement. Le gel possede de bonnes caracteristiques electriques et des proprietes physiques ameliorees ne laissant pas de residus sales sur la peau du patient ou sur l'electrode.An electrically conductive non-sticky cohesive gel facilitates low resistance contact between a metal electrode and a biological body. The gel comprises an aqueous solution having saturation concentrations of ionized salts as a conductive agent, a natural gum capable of crosslinking, and a crosslinking material which gives the electrically conductive gel internal resistance sufficient to keep its cohesion without reinforcement. The gel has good electrical characteristics and improved physical properties, leaving no dirty residue on the patient's skin or on the electrode.
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/072,230 US4406827A (en) | 1979-09-04 | 1979-09-04 | Cohesive nonsticky electrically conductive gel composition |
US72230 | 1979-09-04 |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0035518A1 true EP0035518A1 (en) | 1981-09-16 |
EP0035518A4 EP0035518A4 (en) | 1982-02-05 |
EP0035518B1 EP0035518B1 (en) | 1986-01-22 |
Family
ID=22106350
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP80901684A Expired EP0035518B1 (en) | 1979-09-04 | 1981-03-23 | Cohesive nonsticky electrically conductive gel composition |
Country Status (7)
Country | Link |
---|---|
US (1) | US4406827A (en) |
EP (1) | EP0035518B1 (en) |
JP (1) | JPH0158980B2 (en) |
CA (1) | CA1139931A (en) |
DE (1) | DE3071364D1 (en) |
IT (1) | IT1132636B (en) |
WO (1) | WO1981000785A1 (en) |
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- 1979-09-04 US US06/072,230 patent/US4406827A/en not_active Expired - Lifetime
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1980
- 1980-08-04 DE DE8080901684T patent/DE3071364D1/en not_active Expired
- 1980-08-04 WO PCT/US1980/000988 patent/WO1981000785A1/en active IP Right Grant
- 1980-08-04 JP JP55501987A patent/JPH0158980B2/ja not_active Expired
- 1980-08-05 CA CA000357625A patent/CA1139931A/en not_active Expired
- 1980-09-03 IT IT24439/80A patent/IT1132636B/en active
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1981
- 1981-03-23 EP EP80901684A patent/EP0035518B1/en not_active Expired
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Also Published As
Publication number | Publication date |
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CA1139931A (en) | 1983-01-25 |
IT1132636B (en) | 1986-07-02 |
WO1981000785A1 (en) | 1981-03-19 |
US4406827A (en) | 1983-09-27 |
DE3071364D1 (en) | 1986-03-06 |
EP0035518A4 (en) | 1982-02-05 |
IT8024439A0 (en) | 1980-09-03 |
EP0035518B1 (en) | 1986-01-22 |
JPH0158980B2 (en) | 1989-12-14 |
JPS56501108A (en) | 1981-08-06 |
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